One possible plotline could be that Sakura realizes she has lost her chance with Naruto after he has found love with someone else. She then has to deal with her unrequited love and find a way to move on. Maybe she focuses more on her medical ninja skills and becomes a renowned healer in the village.
Another plot could be set in an alternate universe where Sakura had a chance to confess her true feelings to Naruto earlier but missed it. This leads to a series of events where she tries to make up for that lost opportunity. She might start by doing small things for Naruto like helping him with his training or taking care of him when he's injured, all while trying to find the courage to tell him how she really feels.
Growth and self - discovery are often themes as well. Through the experience of losing her chance with Naruto, Sakura can grow as a person. She might discover new aspects of herself, like her own strength outside of her relationship with Naruto. Maybe she realizes she can be independent and still be happy, even if she can't be with the one she loves.
One possible reason could be that Sakura was too focused on her own goals and neglected her relationship with Naruto. In some fanfics, she might be so driven by her medical ninja career or her need to prove herself that she doesn't give Naruto the attention he needs. Another reason could be that Naruto's own growth and experiences lead him to find someone else more compatible. Maybe he meets a character who understands his pain of being an outcast more deeply, and Sakura just doesn't fit into that new vision of his future.
One possible plotline could be that they discover their relation and then Naruto becomes overprotective of Sakura. Another could be that they have to face some family secrets together. Maybe there's a hidden power in their family that only they can unlock as siblings.
One possible plotline could be Naruto using his second chance to prevent some of the tragedies that occurred in the original story. For example, he might be able to save Jiraiya from his death at the hands of Pain. Another could be that he focuses on training much earlier and more intensively, thus achieving even greater power levels faster. He could also use this second chance to better understand and connect with Sasuke from the start, potentially preventing Sasuke's defection.
Perhaps in the fanfiction, Sakura has been poisoned or affected by a strange jutsu that makes her lose control of her emotions and physical actions. This could lead to her lashing out at Naruto and injuring him. Or it could be that Sakura is in a desperate situation where she believes sacrificing Naruto is the only way to save the greater good. So, she makes a tough decision and injures him in the process. It could also be a part of a training exercise gone wrong. They could be training together and Sakura accidentally uses too much force or a new technique she hasn't fully mastered yet, resulting in Naruto getting injured.
One possible plotline could be Naruto's initial shock and disbelief. He might go through a period of self - doubt, wondering what he did wrong. Another could be his journey to find himself again after such a betrayal. He might focus on his ninja training more intensely to distract himself from the pain.
One possible plotline could be during a powerful enemy attack on the village. Sakura might sacrifice herself to save Naruto and the rest of the village. Maybe she uses all her medical chakra to heal a large number of injured villagers while fending off the enemy at the same time, but in the end, she exhausts herself completely and succumbs to her wounds.
Maybe Sakura is a healer in a small village. A gypsy arrives with a strange illness that no one in the village can cure. Sakura tries her best to help the gypsy, and in the process, she discovers that the gypsy has a unique connection to an ancient magic. This leads Sakura to learn more about this magic from the gypsy, which changes her life and the way she views the world around her.
A plotline could also be that Naruto is lost in space and finds himself on a planet that is in the middle of a magical crisis. Despite not being familiar with the magic there, he uses his ninja spirit and willpower to help. He might team up with a local wizard or sorceress who is impressed by his determination. They would then work together to defeat an evil force that is draining the planet's life force. Naruto's ability to never give up would be a key factor in this adventure.
A possible plotline could be a training arc. Tsunade could be training both Naruto and Sakura in a new and advanced form of combat or medical ninjutsu. This would involve a lot of character development as they struggle to master the new skills. For example, Naruto might have trouble with the precision required in a medical - related technique while Sakura helps him out, and Tsunade observes and gives tough love guidance.